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Nanometer drug-loading system of folic acid-hydroxyalkyl starch macromolecule stable co-loading photosensitizer and micromolecule prodrug, and preparation and application of nanometer drug-loading system

A technology of hydroxyalkyl starch and nano-drug loading, which is applied in multidisciplinary fields, can solve the problems of poor tumor treatment effect and poor stability, achieve good tumor targeting, improve tumor targeting, and improve stability sexual effect

Pending Publication Date: 2022-05-13
HUAZHONG UNIV OF SCI & TECH
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0004] Aiming at the defects of the prior art, the present invention provides a nanometer drug-loading system for stably co-loading a photosensitizer and a hydrophobic small molecule prodrug with a folic acid-hydroxyalkyl starch macromolecular compound, its preparation and application, by using folic acid-hydroxyalkyl starch The alkyl starch macromolecular compound is used as a stabilizer to realize the stable co-loading of the macromolecular compound with the photosensitizer and the hydrophobic small molecule prodrug self-assembled nanoparticle, which effectively solves the problem of the stability of the small molecule prodrug self-assembled nano-drug in the prior art. Poor sex leads to poor technical problems in tumor treatment

Method used

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  • Nanometer drug-loading system of folic acid-hydroxyalkyl starch macromolecule stable co-loading photosensitizer and micromolecule prodrug, and preparation and application of nanometer drug-loading system
  • Nanometer drug-loading system of folic acid-hydroxyalkyl starch macromolecule stable co-loading photosensitizer and micromolecule prodrug, and preparation and application of nanometer drug-loading system
  • Nanometer drug-loading system of folic acid-hydroxyalkyl starch macromolecule stable co-loading photosensitizer and micromolecule prodrug, and preparation and application of nanometer drug-loading system

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preparation example Construction

[0053] The preparation method of the stable co-loaded nano drug-loading system provided by the present invention comprises the following steps:

[0054] (1) mixing the hydrophobic small molecule prodrug and photosensitizer with reduction responsiveness, dialysis after ultrasound, and solid-liquid separation to obtain self-assembled nanoparticles of the doxorubicin dimer prodrug and photosensitizer;

[0055] (2) Mix and stir the self-assembled nanoparticles obtained in step (1) with the folic acid-hydroxyalkyl starch macromolecular compound. After solid-liquid separation, the folic acid-hydroxyalkyl starch macromolecular compound is stably co-loaded with a photosensitizer and has a reduction response. A nano-drug delivery system for hydrophobic small molecule prodrugs.

[0056] In some embodiments, step (1) described solvent comprises organic solvent and ultrapure water, and described organic solvent is DMSO, THF and CH 3 CH 2 One or more of OH. The ultrasonic power of step ...

Embodiment 1

[0062] Preparation and characterization of co-loaded IR780-based DOX-SS-DOX prodrug co-assembled nanoparticles DINs.

[0063] Several nanoparticles with different ratios of IR780 and DOX-SS-DOX were prepared by the solvent replacement method, the specific method is as follows:

[0064] (1) According to the mass ratio of DOX-SS-DOX and IR780 is 0.5:1, 1:1, 2:1 respectively, weigh two kinds of samples. The mass of IR780 is 4mg.

[0065] (2) Add 0.2mL dimethyl sulfoxide to each formula in (1) to dissolve, and then add the samples to 2mL ultrapure water respectively, and ultrasonicate for 5min (150W, 2s / 2s) in an ice-water bath. Take the ultrasonic solution and put it into a dialysis bag (molecular weight cut-off is 3500KDa), put it into ultrapure water and stir for dialysis for 6h, replace it with fresh ultrapure water every 2h, collect the solution in the dialysis bag after dialysis, and centrifuge at 3500rpm for 15min , collect the supernatant. The average particle size of D...

Embodiment 2

[0069] Preparation and Characterization of FDINs Nanoparticles by HES-FA, HES, FA and HES+FA Modification of DINs

[0070] HES-FA means a macromolecular compound obtained by coupling hydroxyethyl starch with a molecular weight of 130KDa and folic acid through an ester bond. The specific preparation method is as follows: folic acid (20mmol, 8.828mg), dicyclohexylcarbodiimidediimide (40mmol, 8.253mg) was dissolved in 10mL dimethylsulfoxide, 4-dimethylaminopyridine (40mmol, 4.887mg) was added, and reacted at 50°C for 30min. Hydroxyethyl starch (1mmol, 130mg) was dissolved in 5mL dimethyl sulfoxide, added to the above reaction system, and continued to react at 50°C for 48h. After the reaction was completed, the reaction solution was added to 100mL ethanol for precipitation, centrifuged at 8000rpm for 10min, and precipitated with dimethyl sulfoxide solvent, placed in a dialysis bag (molecular weight cut-off: 8000Da), dialyzed with ultrapure water for two days, and freeze-dried to o...

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Abstract

The invention belongs to the technical field of multidisciplinary crossing of chemistry, pharmacy, medicine and the like, and particularly relates to a nanometer drug loading system for stably co-loading a photosensitizer and a micromolecule prodrug through folic acid-hydroxyalkyl starch macromolecules, and preparation and application of the nanometer drug loading system. The nano drug delivery system comprises a photosensitizer and self-assembled nanoparticles of a hydrophobic small-molecule prodrug with reduction responsiveness, and further comprises a folic acid-hydroxyalkyl starch macromolecular compound, and experiments show that due to introduction of the folic acid-hydroxyalkyl starch macromolecular compound, the activity of the folic acid-hydroxyalkyl starch macromolecular compound is improved, and the activity of the folic acid-hydroxyalkyl starch macromolecular compound is improved. The stability of the self-assembled nanoparticles of the photosensitizer and the hydrophobic small-molecule prodrug can be remarkably improved, the nano drug-loading system has high drug loading capacity, can maintain long-time stability in a blood environment, remarkably improves tumor targeting, realizes photoacoustic and fluorescence imaging of tumor parts, and has wide application prospects. Meanwhile, the tumor part can be rapidly heated through laser irradiation, the chemotherapy effect of the adriamycin medicine is improved through thermal therapy, and collaborative therapy is achieved.

Description

technical field [0001] The invention belongs to the multidisciplinary technical fields of chemistry, pharmacy, medicine, etc., and more specifically, relates to a nano-drug-loading system for folic acid-hydroxyalkyl starch macromolecules stably co-loading photosensitizers and small-molecule prodrugs, and its preparation and application . Background technique [0002] Tumor is one of the main causes of human death. Chemotherapy is currently one of the most effective means of treating tumors. Although many common chemotherapeutic drugs have certain therapeutic effects, a large number of chemotherapeutic drugs currently on the market still have great defects, such as large toxic and side effects, short blood circulation time, and insufficient accumulation in tumor sites. With the development of science and technology, intelligent prodrug strategies have become one of the important means to solve the existing problems of chemotherapy drugs. By coupling chemotherapy drugs with...

Claims

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Application Information

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IPC IPC(8): A61K47/69A61K47/61A61K41/00A61K47/55A61K49/00A61K49/22A61P35/00B82Y5/00B82Y40/00A61K31/704
CPCA61K47/55A61K41/0057A61K47/61A61K47/6929A61K31/704A61P35/00A61K49/225A61K49/0093A61K49/0054B82Y5/00B82Y40/00
Inventor 李子福杨祥良王冲
Owner HUAZHONG UNIV OF SCI & TECH
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